Clinical outcomes of oral metronomic vinorelbine in advanced non-small cell lung cancer: correlations with pharmacokinetics and MDR1 polymorphisms

Gusella, Milena; Pasini, Felice; Caruso, Donatella; Barile, Carmen; Modena, Yasmina; Fraccon, Anna Paola; Bertolaso, Laura; Menon, Daniela; Crepaldi, Giorgio; Bononi, Antonio; Spezzano, Roberto; Telatin, Giorgia Anna; Corona, Giuseppe; Padrini, Roberto

doi:10.1007/s00280-018-3751-0

Cited by 15 publications

(11 citation statements)

References 23 publications

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“…In conclusion, the combination of oral vinorelbine with erlotinib was feasible and tolerable in both groups. Neither pharmacokinetic nor pharmacogenetic monitoring appeared to be useful in predicting OS with oral metronomic vinorelbine in advanced NSCLC (41). Metronomic vinorelbine inhibited the phosphorylation of extracellular signal-regulated kinase (ERK)1/ERK2 and protein kinase B, and significantly decreased the expression of cyclin-D1 and ATP-binding cassette super-family G member 2 mRNAs and proteins, sensitizing resistant cells to EGFR tyrosine kinase inhibitors (42).…”

Section: Clinical Trials Of Mctmentioning

confidence: 99%

Metronomic chemotherapy in non‑small cell lung cancer (Review)

2020

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Metronomic chemotherapy (MCT) is defined as the rhythmic chemotherapy of low-dose cytotoxic drugs with short or no drug-free breaks over prolonged periods. MCT affects tumor cells and the tumor microenvironment. Particularly, the low-dose schedule impairs the repair process of endothelial cells, resulting in an anti-angiogenesis effect. By stimulating the immune system to eliminate tumor cells, MCT induces immunological activation. Furthermore, combined with targeted therapy, anti-angiogenic drugs enhance the efficacy of MCT. The present review is an overview of phase I, II and III clinical trials focusing on the efficacy, toxicity and mechanism of MCT in patients with non-small cell lung cancer (NSCLC). Furthermore, the prospects of MCT in NSCLC have been discussed. The present review indicated that MCT is an efficacious treatment for selected patients with NSCLC, with acceptable systemic side effects and economic viability for public health. Contents 1. Introduction 2. Preclinical studies of MCT 3. Clinical trials of MCT 4. Mechanism of MCT 5. Conclusion

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Section: Clinical Trials Of Mctmentioning

confidence: 99%

Metronomic chemotherapy in non‑small cell lung cancer (Review)

2020

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“…Median PFS was 3.9 months (range 1–13 months) and median OS reached 8.1 months (range 4.0–24.0+ months) with a 12-month survival rate of 22% ( Figure 1 ). These findings are not surprising as other studies failed to identify correlations between patient outcomes and metronomic oral VNR pharmacokinetics [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 70%

Metronomic oral vinorelbine in patients with advanced non-small cell lung cancer progressing after nivolumab immunotherapy: a retrospective analysis

Gebbia

Aiello

Banna

et al. 2020

ecancer

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Purpose: The availability of immune checkpoint inhibitors has deeply changed the therapeutic scenario of patients with advanced non-small cell lung cancer (NSCLC). Up until now, chemotherapy still represents the first-line treatment for patients with advanced NSCLC not harbouring genetic mutations or lacking high expression of programmed death ligand even if the addition of immunotherapy to first-line chemotherapy has recently been shown to improve clinical outcome. We carried out a multi-institutional retrospective analysis on third-line chemotherapy with metronomic oral vinorelbine (VNR) in a series of patients with metastatic NSCLC pre-treated with first-line chemotherapy and second-line immunotherapy. Patients and methods: Thirty patients with metastatic NSCLC with progressive disease after first-line chemotherapy and subsequent immunotherapy were treated with metronomic oral VNR continuously at the fixed dose of 30 mg three times per week. Results: A partial response was achieved in 4 patients (13.3%), while 10 patients (33.3%) displayed disease stabilisation for an overall disease control rate of 46.7%. Median progression-free survival was 3.9 months (range 1–13 months) and median OS reached 8.1 months (range 4.0–24.0+ months) with a 12-month survival rate of 22%. Conclusion: Oral metronomic VNR appears to be active and safe in patients with metastatic NSCLC in progression after first-line chemotherapy and second-line immunotherapy. The results reported, although from a limited sample, may suggest its use for long-term stabilisation of the disease with good patient compliance.

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“…The severe hematological toxicity (neutropenia grade 4 and anemia grade 2) that the patient developed during treatment with vinorelbine is also interesting, but there was no evidence of association between vinorelbine clearance and CYP3A5*1/*3 genotype or the ABCB1 SNPs tested for [29,30].…”

Section: Discussionmentioning

confidence: 99%

An Example of Personalized Treatment in HR+ HER2+ Long Survivor Breast Cancer Patient (Case Report)

et al. 2021

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Background. Personalized therapy is becoming increasingly popular in oncological scenarios, not only based on molecular pharmacological targets, but also preventing any drug–drug–gene interaction (DDGI), which could lead to severe toxicities. Single nucleotide polymorphisms (SNPs), the individual germline sequence variations in genes involved in drug metabolism, are correlated to interindividual response to drugs and explain both efficacy and toxicity profiles reported by patients. Case presentation. We present the case of a woman suffering from triple-positive breast cancer; she had early-stage disease at the onset and after four years developed metastatic disease. During her history, she presented different toxicities due to antineoplastic treatments. Particularly, hypertransaminasemia was found during every line of treatment. Nevertheless, we were able to guarantee the patient an excellent therapeutic adhesion thanks to the supportive treatments and the reduction of drug dosage. Moreover, we conducted a simultaneous analysis of the patient’s biochemical and genomic data thanks to Drug-PIN software, and we found several significant SNPs of the main enzymes and transporters involved in drug metabolism. Conclusion. Our case report demonstrated the relevance of DDGI in clinical practice management of a patient treated for advanced breast cancer, suggesting the role of Drug-PIN software as an easy-to-use tool to prevent adverse events during cancer treatment and to help physicians in therapeutic algorithms. However, further studies are needed to confirm these results.

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Clinical outcomes of oral metronomic vinorelbine in advanced non-small cell lung cancer: correlations with pharmacokinetics and MDR1 polymorphisms

Cited by 15 publications

References 23 publications

Metronomic chemotherapy in non‑small cell lung cancer (Review)

Metronomic chemotherapy in non‑small cell lung cancer (Review)

Metronomic oral vinorelbine in patients with advanced non-small cell lung cancer progressing after nivolumab immunotherapy: a retrospective analysis

An Example of Personalized Treatment in HR+ HER2+ Long Survivor Breast Cancer Patient (Case Report)

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